The Combined Outcomes of the COVID-19 Pandemic and a Collapsing Economy on Mental Well-Being: A Cross-Sectional Study.

Objective: This study aimed to examine the outcomes of COVID-19 and a collapsing economy on the mental well-being (MWB) of the general Lebanese population. Methods: A cross-sectional study was conducted online in May 2020 and enrolled 502 adults. Results: Mental well-being had a mean of 14.80 (14.37; 15.24). A lower MWB was associated with female gender (beta=-1.533 [-2.324; -0.743]), university education (beta=-2.119 [-3.353;-0.885]), fear of COVID-19 (beta=-0.131 [-0.199; -0.063]), fear of poverty (beta=-0.232 [-0.402;-0.063]), verbal violence at home (beta=-3.464 [-5.137; -1.790]), and chronic disease (beta=-1.307 [-2.283; -0.330]). Better family satisfaction (beta=0.380 [0.235; 0.525]) and better financial situation (beta=0.029 [0.003; 0.055]) were significantly correlated with better MWB. In the subsample of workers/looking for a job, additional factors affected MWB: physical exercise (beta =1.318 [0.370; 2.265]) was associated with better QOL, while being a previous waterpipe smoker, being self-employed before the crisis (beta=-1.22 [-2.208;-0.231]), working from home since the economic crisis (-1.853 [-3.692; -0.013]), and worrying about the long-term effects of the crisis on one's employment status (beta=-0.433 [-0.650; -0.216]) were associated lower MWB. It is noteworthy that closure of the institution yielded a borderline result (B = -1.2; p = .094), while the fear of COVID-19 was not significantly associated with MWB (B = -0.054; p =0.192). Conclusion: This study showed that, during the pandemic, economic and other factors, directly or indirectly related to COVID-19, significantly affected quality of life. The fear of COVID-19 and fear of poverty mainly impacted the MWB of the general population. However, the fear of COVID-19 lost its significance among workers, who reported that factors negatively affecting their MWB are directly related to their employment and the already collapsing economy in Lebanon.

Development and Validation of a Knowledge, Attitude and Practice Questionnaire on Antibiotic Use in Arabic and French Languages in Lebanon.

OBJECTIVES: Validated knowledge-attitude-practice (KAP) questionnaires are essential to design and evaluate intervention programs on antibiotic use. Recently, we validated the first KAP questionnaire on antibiotics in Spain. Cross-cultural adaptation and validation of research tools increase their universal usefulness. Here, we aimed to validate the questionnaire in a developing country with different socioeconomic characteristics from that of Spain. METHODS: We translated the previously developed KAP-questionnaire into Arabic and French, tailored it and then validated it in adult population in Lebanon. The item content validity index (I-CVI), scale content validity index (S-CVI/Ave) and modified Kappa (k*) were calculated. The construct validity of the questionnaire was evaluated using confirmatory factorial analysis (CFA, N = 1460) and its reliability was assessed using intraclass correlation coefficients (ICC, N = 100) and Cronbach's alpha statistic. RESULTS: ICV-I (>0.78), k* (equal to ICV-I for all items) and S-CVI/Ave (≥0.95) confirmed the questionnaire content validity. Pilot testing (N = 40) and face validity showed the understandability of the questionnaire by the population. Test-retest reliability analysis (N = 100) yielded ICC ≥ 0.59 for all knowledge and attitude items, showing the capacity of the questionnaire to generate reproducible results. CFA evidenced adequate fit of the chosen model, thus establishing the construct validity of the questionnaire (root mean squared error approximation = 0.053, standardized root mean square residual = 0.045, comparative fit index = 0.92 and Tucker-Lewis index = 0.90). The questionnaire showed an acceptable internal reliability (Cronbach's alpha = 0.62) and was highly accepted in Lebanon (response rate = 96% and item response rates ≥ 94%). CONCLUSIONS: The validity of the KAP-questionnaire on antibiotics in Arabic and French was demonstrated in Lebanon.

Association of knowledge and attitudes with the misuse of tranquilizers in parents: a study in Beirut (Lebanon).

OBJECTIVE: To measure the association between knowledge, attitudes and practices of personal misuse of tranquilizers among parents of schoolchildren in Beirut (Lebanon). DESIGN: We carried out a cross-sectional study in 1396 adults recruited from parents of students of eleven public and private schools, from primary schools to high schools, using a Knowledge, Attitude and Practices (KAP) questionnaire of personal use of tranquilizers. MAIN OUTCOME MEASURES: We assessed five patterns of tranquilizers' misuse: unprescribed use, shortened treatment, stored leftovers, doubled forgotten doses or taken when remembered, changed dose without medical recommendation, and a sixth composite outcome: 'any misuse'. RESULTS: Sixty-three (62.2%) of 91 parents who used tranquilizers reported at least one misuse pattern. Higher odds of 'any misuse' were observed among parents who reported taking tranquilizers to sleep better, to enjoy themselves with their families or to work better [2.35 ≤ adjusted interquartile odds ratio (aIqOR) ≤ 1.99]. Storing tranquilizers for future need was strongly associated with misuse [aIqOR: 5.00 (95% CI: 3.30, 7.59)]. Greater awareness about hazards of tranquilizers and the importance of therapeutic compliance was associated with lower odds of specific misuse patterns (0.50 ≤ aIqOR ≤ 0.72). CONCLUSIONS: Poor knowledge and medically disapproved attitudes increase the likelihood of practices of tranquilizer misuse.

Validation of the Arabic and French Versions of a Knowledge, Attitudes and Practices (KAP) Questionnaire on Tranquilizer Misuse.

Tranquilizer misuse is an emerging international public health concern. The psychosocial determinants of this misuse remain understudied. Instruments to measure the Knowledge, Attitudes and Practices (KAP) of tranquilizer misuse are unavailable, except for a recently published questionnaire validated in the Spanish language. We translated the KAP questionnaire into Arabic and French, adapted it and undertook a complete validation procedure in the general adult population in Lebanon. The content validity indicators were good: item content validity index ranged between 0.89 and 1.00, the content validity index scale average was ≥0.95 and the modified Kappa statistic for each of the KAP items was equal to I-CVI. The intra-class correlation coefficient values (n = 100) were ≥0.62 for all Knowledge and Attitudes items, demonstrating the item reliability. Confirmatory factorial analysis (n = 1450) showed that the selected model of Knowledge and Attitude constructs has adequate fit indicators and encompassed three factors that showed acceptable internal reliability: Knowledge (Cronbach's alpha = 0.72), personal Attitudes towards tranquilizers (Cronbach's alpha = 0.79) and Attitudes towards healthcare providers (Cronbach's alpha = 0.65). The Arabic/French questionnaire was highly accepted, with a response rate of 95.72% and item non-response rate ≤3.6%. The availability of a cross-cultural adapted and multilingual validated questionnaire would stimulate research on tranquilizer misuse.

The History, Efficacy, and Safety of Potential Therapeutics: A Narrative Overview of the Complex Life of COVID-19.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic posed a serious public health concern and started a race against time for researchers to discover an effective and safe therapy for coronavirus disease 2019 (COVID-19), the disease caused by SARS-CoV-2. This review aims to describe the history, efficacy, and safety of five potential therapeutics for COVID-19, remdesivir, favipiravir, hydroxychloroquine, tocilizumab, and convalescent plasma. A literature review was conducted through October 2020 to identify published studies evaluating the efficacy and safety of these five potential therapeutics. Clinical improvement was used to assess the efficacy, while reported withdrawals from study participation and adverse events were used to evaluate the safety. In total, 95 clinical studies (6 interventional and 89 observational studies) were obtained, of which 42 were included in this review. The evaluation of the efficacy and safety profiles is challenging due to the limitations of the clinical studies on one hand, and the limited number of randomized controlled trials (RCTs) on the other. Moreover, there was insufficient evidence to support repurposing remdesivir, favipiravir, and tocilizumab for COVID-19.

Mental Health Outcomes of the COVID-19 Pandemic and a Collapsing Economy: Perspectives from a Developing Country.

The COVID-19 pandemic has affected physical and mental health worldwide, particularly vulnerable populations with lower social and economic status. This study explored the independent and combined effects of the COVID-19 and economy-related variables on stress and anxiety among Lebanese adults in a developing country facing a severe socio-economic crisis and political turmoil. A cross-sectional study was conducted online between May 10 and 20, 2020, using the snowball sampling technique. All individuals over 18 were eligible. The final sample included 502 respondents. Higher stress and anxiety were associated with younger age, female gender, previous higher socio-economic status, having a family member with a chronic disease, fear of not getting access to treatment, fear of COVID-19, and physical violence at home. However, financial wellness and higher family satisfaction were significantly associated with lower stress. The multivariate analysis showed a significant interaction between fear of COVID-19 and financial wellness on estimated marginal means of stress and anxiety. The combined presence of fear of the pandemic and financial hardship is associated with higher stress and anxiety, particularly among women and younger Lebanese adults with difficult home circumstances. Thus, healthcare professionals need to screen for mental health problems among subgroups presenting multiple risk factors.

Association of knowledge and beliefs with the misuse of antibiotics in parents: A study in Beirut (Lebanon).

BACKGROUND: Antibiotic resistance is a major public health concern. It has been associated with factors such as uncontrolled consumption, lack of knowledge, beliefs, and sociodemographic characteristics. Lebanon is characterized by high levels of antibiotic misuse, as almost half of the population self-medicates with antibiotics and over 30% of the antibiotics are dispensed without prescription. To-date, no studies determined adequately the association between knowledge, beliefs and antibiotic misuse in Lebanon. OBJECTIVE: To assess the association between level of knowledge and beliefs about antibiotics, and antibiotic misuse in Lebanon. METHODS: We conducted a cross-sectional study among 1,421 parents of schoolchildren using an anonymous self-administered Knowledge, Attitude and Practices questionnaire. The participants´ level of agreement with each item of knowledge and beliefs was measured using a Likert-type (0-10) scale. Misuse practices in the last month were detected through a series of questions aimed at determining the level of compliance with physicians´ instructions in terms of dosage and duration. Data were analyzed using logistic regression. RESULTS: 277 participants (16%) acknowledged using antibiotics in the previous month, 41% of whom showed at least one misuse behavior. Misconceptions and beliefs about antibiotics substantially increased the odds of their misuse. For instance, participants who believed that antibiotics were effective in treating viruses, cold, or sore throat infections were twice as likely to misuse antibiotics [Adjusted Interquartile Odds Ratio (aIqOR): 2.08 (95%CI: 1.32, 3.19), aIqOR: 1.81 (95%CI: 1.41, 2.29), aIqOR: 2.19 (95%CI: 1.61, 2.93), respectively]. Parents who usually keep antibiotics at home antibiotics for future use were more likely to misuse antibiotics [aIqOR: 2.44 (95%CI: 1.68, 3.46)]. CONCLUSIONS: Our findings indicate that the low level of knowledge and the existence of erroneous beliefs about antibiotics are associated with increased odds of antibiotic misuse. Key elements including rationale prescription and control of dispensing should be addressed when designing educational campaigns against antibiotic misuse.

Good pharmacy practice assessment among community pharmacies in Lebanon.

OBJECTIVE: This study aims to assess good pharmacy practice (GPP) aspects and compare GPP scores among community pharmacies in Lebanon, using a tool developed jointly by the International Pharmaceutical Federation (FIP) and the World Health Organization (WHO) to improve and maintain standards of pharmacy practice. METHODS: Data collection was carried out between July and October 2018 by a team of 10 licensed inspectors who work at the Lebanese Order of Pharmacists (OPL) and visited community pharmacies across Lebanon. The questionnaire was adapted to the Lebanese context and included 109 questions organized under five sections: socio-demographics, Indicator A (data management and data recording), Indicator B (services and health promotion), Indicator C (dispensing, preparation and administration of medicines), and Indicator D (storage and facilities). The value of 75% was considered as the cutoff point for adherence to indicators. RESULTS: Out of 276 pharmacies visited, a total of 250 (90.58%) pharmacists participated in the study with one pharmacist being interviewed in every pharmacy. Results showed that 18.8% of pharmacists were generally adherents to GPP guidelines (scores above the 75% cutoff): 23.3% were adherent to indicator A, 21.6% to indicator B, 14.8% to indicator C and 13.2% to indicator D. Moreover, comparison of GPP scores across geographical regions revealed a higher adherence among community pharmacists working in the Beirut region compared to the North region, the South region, Mount Lebanon, and the Bekaa. CONCLUSIONS: Our study shows that community pharmacists in Lebanon do not fulfill GPP criteria set by FIP/WHO, and that this poor adherence is a trend across the country's geographical regions. Therefore, efforts should be made to raise awareness among pharmacists about the necessity to adhere to GPP guidelines and standards, and train them and support them appropriately to reach that goal. This is the first indicator-based comprehensive pilot assessment to evaluate GPP adherence in community pharmacies across Lebanon. Working on the optimization of this assessment tool is also warranted.

Good pharmacy practice assessment among community pharmacies in Lebanon

OBJECTIVE: This study aims to assess good pharmacy practice (GPP) aspects and compare GPP scores among community pharmacies in Lebanon, using a tool developed jointly by the International Pharmaceutical Federation (FIP) and the World Health Organization (WHO) to improve and maintain standards of pharmacy practice. METHODS: Data collection was carried out between July and October 2018 by a team of 10 licensed inspectors who work at the Lebanese Order of Pharmacists (OPL) and visited community pharmacies across Lebanon. The questionnaire was adapted to the Lebanese context and included 109 questions organized under five sections: socio-demographics, Indicator A (data management and data recording), Indicator B (services and health promotion), Indicator C (dispensing, preparation and administration of medicines), and Indicator D (storage and facilities). The value of 75% was considered as the cutoff point for adherence to indicators. RESULTS: Out of 276 pharmacies visited, a total of 250 (90.58%) pharmacists participated in the study with one pharmacist being interviewed in every pharmacy. Results showed that 18.8% of pharmacists were generally adherents to GPP guidelines (scores above the 75% cutoff): 23.3% were adherent to indicator A, 21.6% to indicator B, 14.8% to indicator C and 13.2% to indicator D. Moreover, comparison of GPP scores across geographical regions revealed a higher adherence among community pharmacists working in the Beirut region compared to the North region, the South region, Mount Lebanon, and the Bekaa. CONCLUSIONS: Our study shows that community pharmacists in Lebanon do not fulfill GPP criteria set by FIP/WHO, and that this poor adherence is a trend across the country's geographical regions. Therefore, efforts should be made to raise awareness among pharmacists about the necessity to adhere to GPP guidelines and standards, and train them and support them appropriately to reach that goal. This is the first indicator-based comprehensive pilot assessment to evaluate GPP adherence in community pharmacies across Lebanon. Working on the optimization of this assessment tool is also warranted

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p53 Restoration in Induction and Maintenance of Senescence: Differential Effects in Premalignant and Malignant Tumor Cells.

The restoration of p53 has been suggested as a therapeutic approach in tumors. However, the timing of p53 restoration in relation to its efficacy during tumor progression still is unclear. We now show that the restoration of p53 in murine premalignant proliferating pineal lesions resulted in cellular senescence, while p53 restoration in invasive pineal tumors did not. The effectiveness of p53 restoration was not dependent on p19(Arf) expression but showed an inverse correlation with Mdm2 expression. In tumor cells, p53 restoration became effective when paired with either DNA-damaging therapy or with nutlin, an inhibitor of p53-Mdm2 interaction. Interestingly, the inactivation of p53 after senescence resulted in reentry into the cell cycle and rapid tumor progression. The evaluation of a panel of human supratentorial primitive neuroectodermal tumors (sPNET) showed low activity of the p53 pathway. Together, these data suggest that the restoration of the p53 pathway has different effects in premalignant versus invasive pineal tumors, and that p53 activation needs to be continually sustained, as reversion from senescence occurs rapidly with aggressive tumor growth when p53 is lost again. Finally, p53 restoration approaches may be worth exploring in sPNET, where the p53 gene is intact but the pathway is inactive in the majority of examined tumors.

WT1 controls antagonistic FGF and BMP-pSMAD pathways in early renal progenitors.

Kidney organogenesis requires the tight control of proliferation, differentiation and apoptosis of renal progenitor cells. How the balance between these cellular decisions is achieved remains elusive. The Wilms' tumour suppressor Wt1 is required for progenitor survival, but the molecular cause for renal agenesis in mutants is poorly understood. Here we demonstrate that lack of Wt1 abolishes fibroblast growth factor (FGF) and induces BMP/pSMAD signalling within the metanephric mesenchyme. Addition of recombinant FGFs or inhibition of pSMAD signalling rescues progenitor cell apoptosis induced by the loss of Wt1. We further show that recombinant BMP4, but not BMP7, induces an apoptotic response within the early kidney that can be suppressed by simultaneous addition of FGFs. These data reveal a hitherto unknown sensitivity of early renal progenitors to pSMAD signalling, establishes FGF and pSMAD signalling as antagonistic forces in early kidney development and places WT1 as a key regulator of pro-survival FGF signalling pathway genes.

Y-chromosome and mtDNA genetics reveal significant contrasts in affinities of modern Middle Eastern populations with European and African populations.

The Middle East was a funnel of human expansion out of Africa, a staging area for the Neolithic Agricultural Revolution, and the home to some of the earliest world empires. Post LGM expansions into the region and subsequent population movements created a striking genetic mosaic with distinct sex-based genetic differentiation. While prior studies have examined the mtDNA and Y-chromosome contrast in focal populations in the Middle East, none have undertaken a broad-spectrum survey including North and sub-Saharan Africa, Europe, and Middle Eastern populations. In this study 5,174 mtDNA and 4,658 Y-chromosome samples were investigated using PCA, MDS, mean-linkage clustering, AMOVA, and Fisher exact tests of F(ST)'s, R(ST)'s, and haplogroup frequencies. Geographic differentiation in affinities of Middle Eastern populations with Africa and Europe showed distinct contrasts between mtDNA and Y-chromosome data. Specifically, Lebanon's mtDNA shows a very strong association to Europe, while Yemen shows very strong affinity with Egypt and North and East Africa. Previous Y-chromosome results showed a Levantine coastal-inland contrast marked by J1 and J2, and a very strong North African component was evident throughout the Middle East. Neither of these patterns were observed in the mtDNA. While J2 has penetrated into Europe, the pattern of Y-chromosome diversity in Lebanon does not show the widespread affinities with Europe indicated by the mtDNA data. Lastly, while each population shows evidence of connections with expansions that now define the Middle East, Africa, and Europe, many of the populations in the Middle East show distinctive mtDNA and Y-haplogroup characteristics that indicate long standing settlement with relatively little impact from and movement into other populations.

RNA: a possible contributor to the 'missing heritability'.

A number of human pathologies have a transmission pattern that does not obey Mendelian segregation rules. This type of heredity is defined as non-Mendelian and is based on mechanisms of transgenerational epigenetic inheritance. Comprehensive information on the molecular mechanisms of it is still lacking. However, recent evidence from distantly related species including Caenorhabditis elegans, Drosophila, and mouse, points towards a role for non-coding RNA molecules in such a pattern of inheritance. While it would be too hasty to conclude that RNA molecules are at work in the transgenerational non-genetic inheritance of human pathologies, a growing number of studies seem to strongly support such a speculation.

De nombreuses études scientifiques ont clairement établi que nos différentes expériences de vie, notamment notre alimentation, ont un impact crucial sur l'expression de nos gènes, ainsi que sur celle de notre descendance. Le plus souvent, la transmission de telle maladie et/ou de tel phénotype nouvellement acquis ne suit pas les lois de Mendel et est souvent associée à des altérations non génétiques. Cette hérédité, dite hérédité épigénétique, est encore très mal connue sur le plan moléculaire. Néanmoins, de nombreuses analyses réalisées sur des organismes très éloignés sur le plan évolutif, allant du nématode C. elegans à la souris, en passant par la mouche Drosophile, montrent que les molécules d'ARN fournies par le gamète à l'embryon y joueraient un rôle déterminant. Bien qu'il soit prématuré de confirmer que les molécules d'ARN pourraient jouer le même rôle dans la transmission de certaines pathologies humaines, l'ensemble de ces données tend à montrer que cela pourrait bien être le cas.

Genome-wide association study in a Lebanese cohort confirms PHACTR1 as a major determinant of coronary artery stenosis.

The manifestation of coronary artery disease (CAD) follows a well-choreographed series of events that includes damage of arterial endothelial cells and deposition of lipids in the sub-endothelial layers. Genome-wide association studies (GWAS) of multiple populations with distinctive genetic and lifestyle backgrounds are a crucial step in understanding global CAD pathophysiology. In this study, we report a GWAS on the genetic basis of arterial stenosis as measured by cardiac catheterization in a Lebanese population. The locus of the phosphatase and actin regulator 1 gene (PHACTR1) showed association with coronary stenosis in a discovery experiment with genome wide data in 1,949 individuals (rs9349379, OR = 1.37, p = 1.57×10(-5)). The association was replicated in an additional 2,547 individuals (OR = 1.31, p = 8.85×10(-6)), leading to genome-wide significant association in a combined analysis (OR = 1.34, p = 8.02×10(-10)). Results from this GWAS support a central role of PHACTR1 in CAD susceptibility irrespective of lifestyle and ethnic divergences. This association provides a plausible component for understanding molecular mechanisms involved in the formation of stenosis in cardiac vessels and a potential drug target against CAD.

Genetic and environmental influences on total plasma homocysteine and its role in coronary artery disease risk.

BACKGROUND: Elevated levels of total plasma homocysteine are a risk factor for atherosclerotic disease. AIMS: The rationale behind this study is to explore the correlation between degree and site of coronary lesion and hyperhomocysteinemia in Lebanese CAD patients and assess environmental and genetic factors for elevated levels of total plasma homocysteine. METHODS: A total of 2644 patients were analyzed for traditional CAD risk factors. Logistic regression was performed to determine the association of hyperhomocysteinemia with degree and site of coronary lesions controlling for risk factors. Environmental and genetic factors for hyperhomocysteinemia were analyzed by logistic regression using a candidate gene approach. RESULTS: Traditional risk factors were correlated with stenosis. Hyperhomocysteinemia associated with increased risk of overall stenosis, and risk of mild and severe occlusion in major arteries. Hyperhomocysteinemia and hypertension were highly correlated suggesting that hyperhomocysteinemia acts as a hypertensive agent leading to CAD. Diuretics and genetic polymorphisms in MTHFR and SLCO1B1 were associated with hyperhomocysteinemia. CONCLUSIONS: Hyperhomocysteinemia is a medical indicator of specific vessel stenosis in the Lebanese population. Hypertension is a major link between hyperhomocysteinemia and CAD occurrence. Genetic polymorphisms and diuretics' intake explain partly elevated homocysteine levels. This study has important implications in CAD risk prediction.

Y-chromosome R-M343 African lineages and sickle cell disease reveal structured assimilation in Lebanon.

We have sought to identify signals of assimilation of African male lines in Lebanon by exploring the association of sickle cell disease (SCD) in Lebanon with Y-chromosome haplogroups that are informative of the disease origin and its exclusivity to the Muslim community. A total of 732 samples were analyzed, including 33 SCD patients from Lebanon genotyped for 28 binary markers and 19 short tandem repeats on the non-recombinant segment of the Y chromosome. Genetic organization was identified using populations known to have influenced the genetic structure of the Lebanese population, in addition to African populations with high incidence of SCD. Y-chromosome haplogroup R-M343 sub-lineages distinguish between sub-Saharan African and Lebanese Y chromosomes. We detected a limited penetration of SCD into Lebanese R-M343 carriers, restricted to Lebanese Muslims. We suggest that this penetration brought the sickle cell gene along with the African R-M343, probably with the Saharan caravan slave trade.

Influences of history, geography, and religion on genetic structure: the Maronites in Lebanon.

Cultural expansions, including of religions, frequently leave genetic traces of differentiation and in-migration. These expansions may be driven by complex doctrinal differentiation, together with major population migrations and gene flow. The aim of this study was to explore the genetic signature of the establishment of religious communities in a region where some of the most influential religions originated, using the Y chromosome as an informative male-lineage marker. A total of 3139 samples were analyzed, including 647 Lebanese and Iranian samples newly genotyped for 28 binary markers and 19 short tandem repeats on the non-recombinant segment of the Y chromosome. Genetic organization was identified by geography and religion across Lebanon in the context of surrounding populations important in the expansions of the major sects of Lebanon, including Italy, Turkey, the Balkans, Syria, and Iran by employing principal component analysis, multidimensional scaling, and AMOVA. Timing of population differentiations was estimated using BATWING, in comparison with dates of historical religious events to determine if these differentiations could be caused by religious conversion, or rather, whether religious conversion was facilitated within already differentiated populations. Our analysis shows that the great religions in Lebanon were adopted within already distinguishable communities. Once religious affiliations were established, subsequent genetic signatures of the older differentiations were reinforced. Post-establishment differentiations are most plausibly explained by migrations of peoples seeking refuge to avoid the turmoil of major historical events.

Large scale association analysis identifies three susceptibility loci for coronary artery disease.

Genome wide association studies (GWAS) and their replications that have associated DNA variants with myocardial infarction (MI) and/or coronary artery disease (CAD) are predominantly based on populations of European or Eastern Asian descent. Replication of the most significantly associated polymorphisms in multiple populations with distinctive genetic backgrounds and lifestyles is crucial to the understanding of the pathophysiology of a multifactorial disease like CAD. We have used our Lebanese cohort to perform a replication study of nine previously identified CAD/MI susceptibility loci (LTA, CDKN2A-CDKN2B, CELSR2-PSRC1-SORT1, CXCL12, MTHFD1L, WDR12, PCSK9, SH2B3, and SLC22A3), and 88 genes in related phenotypes. The study was conducted on 2,002 patients with detailed demographic, clinical characteristics, and cardiac catheterization results. One marker, rs6922269, in MTHFD1L was significantly protective against MI (OR=0.68, p=0.0035), while the variant rs4977574 in CDKN2A-CDKN2B was significantly associated with MI (OR=1.33, p=0.0086). Associations were detected after adjustment for family history of CAD, gender, hypertension, hyperlipidemia, diabetes, and smoking. The parallel study of 88 previously published genes in related phenotypes encompassed 20,225 markers, three quarters of which with imputed genotypes The study was based on our genome-wide genotype data set, with imputation across the whole genome to HapMap II release 22 using HapMap CEU population as a reference. Analysis was conducted on both the genotyped and imputed variants in the 88 regions covering selected genes. This approach replicated HNRNPA3P1-CXCL12 association with CAD and identified new significant associations of CDKAL1, ST6GAL1, and PTPRD with CAD. Our study provides evidence for the importance of the multifactorial aspect of CAD/MI and describes genes predisposing to their etiology.